Studies conducted on isotretinoin have shown that it may indirectly lead to atherosclerosis. The objective of this study was to determine the effect of systemic isotretinoin on subclinical atherosclerosis. The present study included 63 patients with acne vulgaris who had used isotretinoin for 6 months. Glucose, insulin, and homeostatic model assessment of insulin resistance levels; body mass index; waist circumference; blood pressure; lipid profile; and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), high-sensitivity C-reactive protein, and oxidized low-density lipoprotein (Ox-LDL) levels were compared in the patients at the initiation and discontinuation of the treatment. At the discontinuation of the treatment, LOX-1 and Ox-LDL levels showed a significant increase (P < 0.001 and P = 0.040, respectively). Differences in waist circumference were positively correlated with an increase in LOX-1 levels (r = 0.274; P = 0.030). Isotretinoin causes an increase in the levels of subclinical atherosclerosis markers. Although the present study sample size was small, we believe that caution should be exercised considering the risk of atherosclerosis during isotretinoin use in men with high waist circumference and cardiovascular risk factors; further studies are warranted in this regard. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.